Episodic memory ERPs reflect preclinical Alzheimer’s disease progression

Abstract

Background Alzheimer’s disease (AD) neuropathology emerges decades before symptoms, requiring sensitive, non-invasive markers for early diagnosis. We investigated behavioural and EEG markers of episodic memory in cognitively normal older adults at-risk for AD. Methods Forty-five INSIGHT-preAD cohort participants (15 progressors to prodromal AD, 15 stable β-amyloid positive [Aβ+] participants, 15 controls [Aβ-]) completed an Old/New word recognition task during high-density EEG. Behavioural performance and memory-related evoked-related potentials (ERPs; P3, FN400, P600, post-retrieval monitoring) were analysed longitudinally over 5 years. Results Progressors showed significantly reduced accuracy, sensitivity, and slower responses. They showed attenuated FN400, P600, and monitoring amplitudes over left parieto-occipital regions. Source analysis revealed hypoactivation in the left inferior frontal and right posterior cingulate cortex, across components with additional disruption during P600. Stable Aβ+ individuals showed milder P600 hypoactivations. Discussion Behavioural and ERP alterations preceded clinical decline, supporting EEG-based markers of episodic memory decline for preclinical AD risk stratification.